This proposal represents a continuation of studies of perfusion and function of the hypertrophied left ventricle. Pressure-overload hypertrophy will be produced by banding the ascending aorta or by aortic valve plication in dogs 7-8 weeks of age; studies will be performed at one year of age. Animals with perinephritic hypertension will also be studied. Chronically instrumented animals will be studied in the awake state; regional myocardial blood flow will be measured with microspheres while a coronary sinus catheter will allow measurement of myocardial oxygen extraction, and detection of lactate and adenosine metabolites as indicators of ischemia. The following questions will be examined using these experimental models: (1) Does the exaggerated increase in left ventricular systolic pressure during exercise in the presence of left ventricular outflow obstruction result in an abnormally great increase in myocardial oxygen requirements, and contribute to development of myocardial ischemia? Does the differing coronary hemodynamics of the three models of hypertrophy influence myocardial perfusion during exercise? (2) Does abnormal myocardial perfusion in the hypertrophied heart during tachycardia result from increased extravascular forces acting on the intramural coronary vessels or from neurogenic coronary vasoconstriction? Does regional left ventricular denervation by epicardial application of phenyl or alpha-adrenergic blockade enhance myocardial perfusion? (3) Does exercise training increase the degree of hypertrophy in the pressure-overloaded left ventricle, and does exercise exert a beneficial effect on the coronary vascular system, as manifested by increased vessel diameter, decreased intercapillary distance, and decreased minimum coronary vascular resistance? (4) Is the failure of arterial pressure to increase during exercise in the presence of aortic stenosis the result of activation of left ventricular baroreceptors? Does blockade of left ventricular receptors by intrapericardial procaine or vagal cold block normalize the response of arterial blood pressure and organ blood flow during exercise in dogs with aortic stenosis? (5) Does pacing-induced tachycardia cause decreased diastolic compliance in the hypertrophied left ventricle? Is decreased compliance in response to tachycardia the result of subendocardial ischemia? Does nifedipine improve diastolic compliance of the hypertrophied left ventricle by enhancing blood flow or by a direct effect on the myocardium?